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Ovarian adenocarcinoma presenting with the sign of Leser-Trélat
GYNECOLOGIC ONCOLOGY 25,
128-132 (1986)
Ovarian Adenocarcinoma Presenting with the Sign of Leser-Trklat THERESE HOLGUIN, M.D., R. STEVEN PADILLA, AND FRANCISCO AMPUERO, M.D.* Department
M.D.,
of Dermatology and the *Division of Gynecologic Oncology, University Mexico, School of Medicine and Cancer Center, 2701 Frontier N.E., Albuquerque, New Mexico 87131
of New
Received May 22, 1985 A 76-year-old woman with ovarian adenocarcinoma and sudden onset of many seborrheic keratoses is reported. This cutaneous sign, a marker of an internal malignancy, is known as the sign of Leser-Trelat. Its association with gynecotogic neoplasms is reviewed. o 1986 Academic Press, Inc.
INTRODUCTION The sign of Leser-Trelat (LT) is the sudden onset and rapid increase in size of numerous seborrheic keratoses in association with occult malignancy [l]. A recent review on this subject found only 23 reported cases [2]. We describe a patient with ovarian adenocarcinoma who initially presented with the sign of LT. The gynecologic neoplasms associated with this sign are reviewed. CASE DESCRIPTION A 76-year-old GSP2female was first seen in the spring of 1982by a dermatologist. She complained that during a several-week period she developed dark “itchy growths” on her skin. Cutaneous examination revealed more than 1000 seborrheic keratoses, ranging in size from 0.1 mm to 2.0 cm. The keratoses were described as pruritic and present over her entire body sparing only her palms and soles (Figs. 1 and 2). A skin biopsy was interpreted as a seborrheic keratosis (Fig. 3). There was mild diffuse scalp alopecia with the mucous membranes having a seborrheic keratosis-like growth on her lower gingiva. A diagnosis of seborrheic keratoses with consideration of the sign of LT was made and the patient referred for gynecologic exam. Her pelvic examination was within normal limits. However, her PAP smear revealed cervical dysplasia. Subsequent colposcopy and cervical biopsies demonstrated moderate cervical dysplasia (CIN II), which was treated by cryosurgery. Repeat PAP in May of 1982 was interpreted as Class II without evidence of dysplasia and the patient released to return for follow-up in 6 months. Her cutaneous findings were unchanged. In December 1982 she was hospitalized for evaluation of a 20-pound weight loss with continued and increasing number of skin lesions. Systemic complaints included hair loss, nail splitting, abdominal bloating, belching, flatulence, nausea, 128 0090-8258/86 $1.50 Copyright 0 1986 by Academic Press, Inc. All rights of reproduction in any form reserved
CASE
FIG.
REPORTS
129
1. Chest photograph showing numerous seborrheic keratoses.
and a recent onset of constipation. Pelvic examination revealed a right-sided irregular uterine mass. The remainder of her physical exam was within normal limits except for hepatomegaly. Pelvic ultrasound demonstrated a right adnexal mass. Examination under general anesthesia revealed a cul-de-sac nodularity that measured 4.0 x 4.0 x 3.0 cm and a right-sided ovarian mass with pyometrium. Endometrial curettings and biopsy samples were interpreted as negative for malignant cells. In March of 1983 she underwent a total abdominal hysterectomy, bilateral salpingo-oopherectomy, omentectomy, and node sampling. Microscopic examination of the ovary revealed a poorly differentiated adenocarcinoma, FIG0 Grade III, with metastases to the left ovary, fallopian tubes, uterine fundus, and paraaortic lymphatic chain. DISCUSSION The sign of LT is a rare but reliable cutaneous marker of internal malignancy. In addition to this sign, acanthosis nigricans (AN), a distinctive velvety hyperpigmented verrucous plaque predominantly of the axillae and flexural regions, is considered a marker that has been associated with internal malignancy when occurring in adults [3]. AN, florid cutaneous papillomatosis, and the sign of LT may occur simultaneously or in any combination [ 1,4-71. Some authors consider the sign of LT a variant form of AN. The onset of the sign of LT is characterized as “sudden” with most reports describing their development within a period of weeks to several months [2]. In most cases the clinical course of the keratoses appears to parallel the cancer in regards to growth or remission. They have been reported to occur during or after chemotherapy [t]. Response to chemotherapy is variable, and it is not
130
HOLGUIN,
FIG. 2.
PADILLA,
AND
AMPUERO
Lower extremities showing numerous seborrheic ke:ral
131
CASE REPORTS
known whether in some instances of their regression that they recede on the basis of direct action from the drug or as a result of tumor destruction. Nevertheless, it has been proposed that by following these cutaneous findings one may be able to judge the response of the tumor to treatment. Our patient presented with what is described as the sign of LT without evidence of AN. To the best of our knowledge, there are no additional case reports of ovarian neoplasms presenting with the sign of LT. The many theories about the cause of the sign of LT are still controversial. Most reports of malignancies with this sign have been associated with adenocarcinomas [l-7,9]. The most prominent theory is that these glandular carcinomas produce and secrete peptides that are chemically similar to epidermal growth factor which is known to cause epidermal proliferation. Some elevations in epidermal growth factor have been documented in patients presenting with the sign of LT. On the other hand, one investigator feels that the relationship between the sign of LT and malignancy is questionable because seborrheic keratoses are often found in the elderly who have an increased incidence of neoplasm [lo]. Additional gynecologic neoplasms reported to occur with the sign of LT are listed in Table 1. It is interesting to note that many of these cases have also presented with AN. TABLE GYNECOLOGK
Site of neoplasm Ovary
Reference
Skin histology”
Tumor histology
Associated syndromeb
SK, P
Adenocarcinoma
LT
[31
SK, *
AN
AN
[51
SK, AN, AN, AN, AN, SK,
AN
Adenocarcinoma (metastases) Adenocarcinoma
*
AN AN AN LT
[71
P CW * * * AN,
* * * SK, P
[Ill
freckles AN, * AN, * AN, * AN, * AN, * AN, * AN, * AN, * AN, * AN, * AN, *
* * * * * * * * * * *
WI
AN, P
*
[31 131 131 [31 [31 [31 [31 [31 [31 [Ill
Cervix
Clinical findings” SK, CW
Present report
[I [ill illI Uterus
1
NEOPLASMS ASSOCIATED WITH THE SIGN OF LESER-TR~LAT
Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma *
* * * * * * Squamous cell *
a SK, seborrheic keratoses, P, papillomatosis, AN, nigricans, CW, common wart. ’ LT, Leser-TrClat, AN, acanthosis nigricans. * Findings not mentioned.
AN
AN AN AN AN AN AN AN AN AN AN AN AN
132
HOLGUIN,
PADILLA,
AND
AMPUERO
In conclusion, our case documents the onset of the sign of LT and its usefulness as a marker of occult malignancy. The little-known association of gynecologic malignancies with the sign of LT is reported. REFERENCES 1. Schwartz, R. A., Acanthosis nigricans, florid cutaneous papillomatosis and the sign of LeserTrelat, Cutis 28, 319-322, 326-327, 330-331 (1981). 2. Venencie, P. Y., and Perry, H. O., Sign of Leser-Trelat: Report of two cases and review of the literature, J. Amer. Acad. Dermatol. 10, 83-88 (1984). 3. Curth, H. O., Cancer associated with acanthosis nigricans, Arch. Surg. 47, 517-554 (1943). 4. Dantzig, P. L., Sign of Leser-Trelat, Arch. Dermatol. 108, 700-701 (1973). 5. Dingley, E. R., and Martin, R. H., Adenocarcinoma of the ovary presenting as acanthosis nigricans, J. Obstet. Gynaecol. En’?. Emp. 64, 898-900 (1957). 6. Sneddon, I. B., and Roberts, J. B. M., An incomplete form of acanthosis nigricans, Gut 3, 269701 (1962). 7. Ronchese, F., Keratoses, cancer and “the sign of Leser-Trelat,” Cancer 18, 1003-1006 (1965). 8. Smally, S. R., Rubin, J., and Leiferman, K. M., Neurofibrosarcoma and the sign of LeserTrClat, Ca 34, 295-298 (1984). 9. Rigel, D. S., and Jacobs, M. I., Malignant acanthosis nigricans: A review, J. Dermatol. Surg. Oncol. 6, 923-927 (1980). 10. Kierland, R., Cutaneous signs of internal malignancy, South. Med. J. 65, 563-568 (1972). 11. Curth, H. O., Hilberg, H. W., and Machacek, G. F., The site and histology of the cancer associated with malignant acanthosis nigricans, Cancer 15, 364 (1962). 12. Ive, F. A., Metastatic carcinoma cervix with acanthosis nigricans, bullous pemphigoid and hypertrophic pulmonary osteoarthropathy, Proc. R. Sot. Med. 56, 910 (1963).
128-132 (1986)
Ovarian Adenocarcinoma Presenting with the Sign of Leser-Trklat THERESE HOLGUIN, M.D., R. STEVEN PADILLA, AND FRANCISCO AMPUERO, M.D.* Department
M.D.,
of Dermatology and the *Division of Gynecologic Oncology, University Mexico, School of Medicine and Cancer Center, 2701 Frontier N.E., Albuquerque, New Mexico 87131
of New
Received May 22, 1985 A 76-year-old woman with ovarian adenocarcinoma and sudden onset of many seborrheic keratoses is reported. This cutaneous sign, a marker of an internal malignancy, is known as the sign of Leser-Trelat. Its association with gynecotogic neoplasms is reviewed. o 1986 Academic Press, Inc.
INTRODUCTION The sign of Leser-Trelat (LT) is the sudden onset and rapid increase in size of numerous seborrheic keratoses in association with occult malignancy [l]. A recent review on this subject found only 23 reported cases [2]. We describe a patient with ovarian adenocarcinoma who initially presented with the sign of LT. The gynecologic neoplasms associated with this sign are reviewed. CASE DESCRIPTION A 76-year-old GSP2female was first seen in the spring of 1982by a dermatologist. She complained that during a several-week period she developed dark “itchy growths” on her skin. Cutaneous examination revealed more than 1000 seborrheic keratoses, ranging in size from 0.1 mm to 2.0 cm. The keratoses were described as pruritic and present over her entire body sparing only her palms and soles (Figs. 1 and 2). A skin biopsy was interpreted as a seborrheic keratosis (Fig. 3). There was mild diffuse scalp alopecia with the mucous membranes having a seborrheic keratosis-like growth on her lower gingiva. A diagnosis of seborrheic keratoses with consideration of the sign of LT was made and the patient referred for gynecologic exam. Her pelvic examination was within normal limits. However, her PAP smear revealed cervical dysplasia. Subsequent colposcopy and cervical biopsies demonstrated moderate cervical dysplasia (CIN II), which was treated by cryosurgery. Repeat PAP in May of 1982 was interpreted as Class II without evidence of dysplasia and the patient released to return for follow-up in 6 months. Her cutaneous findings were unchanged. In December 1982 she was hospitalized for evaluation of a 20-pound weight loss with continued and increasing number of skin lesions. Systemic complaints included hair loss, nail splitting, abdominal bloating, belching, flatulence, nausea, 128 0090-8258/86 $1.50 Copyright 0 1986 by Academic Press, Inc. All rights of reproduction in any form reserved
CASE
FIG.
REPORTS
129
1. Chest photograph showing numerous seborrheic keratoses.
and a recent onset of constipation. Pelvic examination revealed a right-sided irregular uterine mass. The remainder of her physical exam was within normal limits except for hepatomegaly. Pelvic ultrasound demonstrated a right adnexal mass. Examination under general anesthesia revealed a cul-de-sac nodularity that measured 4.0 x 4.0 x 3.0 cm and a right-sided ovarian mass with pyometrium. Endometrial curettings and biopsy samples were interpreted as negative for malignant cells. In March of 1983 she underwent a total abdominal hysterectomy, bilateral salpingo-oopherectomy, omentectomy, and node sampling. Microscopic examination of the ovary revealed a poorly differentiated adenocarcinoma, FIG0 Grade III, with metastases to the left ovary, fallopian tubes, uterine fundus, and paraaortic lymphatic chain. DISCUSSION The sign of LT is a rare but reliable cutaneous marker of internal malignancy. In addition to this sign, acanthosis nigricans (AN), a distinctive velvety hyperpigmented verrucous plaque predominantly of the axillae and flexural regions, is considered a marker that has been associated with internal malignancy when occurring in adults [3]. AN, florid cutaneous papillomatosis, and the sign of LT may occur simultaneously or in any combination [ 1,4-71. Some authors consider the sign of LT a variant form of AN. The onset of the sign of LT is characterized as “sudden” with most reports describing their development within a period of weeks to several months [2]. In most cases the clinical course of the keratoses appears to parallel the cancer in regards to growth or remission. They have been reported to occur during or after chemotherapy [t]. Response to chemotherapy is variable, and it is not
130
HOLGUIN,
FIG. 2.
PADILLA,
AND
AMPUERO
Lower extremities showing numerous seborrheic ke:ral
131
CASE REPORTS
known whether in some instances of their regression that they recede on the basis of direct action from the drug or as a result of tumor destruction. Nevertheless, it has been proposed that by following these cutaneous findings one may be able to judge the response of the tumor to treatment. Our patient presented with what is described as the sign of LT without evidence of AN. To the best of our knowledge, there are no additional case reports of ovarian neoplasms presenting with the sign of LT. The many theories about the cause of the sign of LT are still controversial. Most reports of malignancies with this sign have been associated with adenocarcinomas [l-7,9]. The most prominent theory is that these glandular carcinomas produce and secrete peptides that are chemically similar to epidermal growth factor which is known to cause epidermal proliferation. Some elevations in epidermal growth factor have been documented in patients presenting with the sign of LT. On the other hand, one investigator feels that the relationship between the sign of LT and malignancy is questionable because seborrheic keratoses are often found in the elderly who have an increased incidence of neoplasm [lo]. Additional gynecologic neoplasms reported to occur with the sign of LT are listed in Table 1. It is interesting to note that many of these cases have also presented with AN. TABLE GYNECOLOGK
Site of neoplasm Ovary
Reference
Skin histology”
Tumor histology
Associated syndromeb
SK, P
Adenocarcinoma
LT
[31
SK, *
AN
AN
[51
SK, AN, AN, AN, AN, SK,
AN
Adenocarcinoma (metastases) Adenocarcinoma
*
AN AN AN LT
[71
P CW * * * AN,
* * * SK, P
[Ill
freckles AN, * AN, * AN, * AN, * AN, * AN, * AN, * AN, * AN, * AN, * AN, *
* * * * * * * * * * *
WI
AN, P
*
[31 131 131 [31 [31 [31 [31 [31 [31 [Ill
Cervix
Clinical findings” SK, CW
Present report
[I [ill illI Uterus
1
NEOPLASMS ASSOCIATED WITH THE SIGN OF LESER-TR~LAT
Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma *
* * * * * * Squamous cell *
a SK, seborrheic keratoses, P, papillomatosis, AN, nigricans, CW, common wart. ’ LT, Leser-TrClat, AN, acanthosis nigricans. * Findings not mentioned.
AN
AN AN AN AN AN AN AN AN AN AN AN AN
132
HOLGUIN,
PADILLA,
AND
AMPUERO
In conclusion, our case documents the onset of the sign of LT and its usefulness as a marker of occult malignancy. The little-known association of gynecologic malignancies with the sign of LT is reported. REFERENCES 1. Schwartz, R. A., Acanthosis nigricans, florid cutaneous papillomatosis and the sign of LeserTrelat, Cutis 28, 319-322, 326-327, 330-331 (1981). 2. Venencie, P. Y., and Perry, H. O., Sign of Leser-Trelat: Report of two cases and review of the literature, J. Amer. Acad. Dermatol. 10, 83-88 (1984). 3. Curth, H. O., Cancer associated with acanthosis nigricans, Arch. Surg. 47, 517-554 (1943). 4. Dantzig, P. L., Sign of Leser-Trelat, Arch. Dermatol. 108, 700-701 (1973). 5. Dingley, E. R., and Martin, R. H., Adenocarcinoma of the ovary presenting as acanthosis nigricans, J. Obstet. Gynaecol. En’?. Emp. 64, 898-900 (1957). 6. Sneddon, I. B., and Roberts, J. B. M., An incomplete form of acanthosis nigricans, Gut 3, 269701 (1962). 7. Ronchese, F., Keratoses, cancer and “the sign of Leser-Trelat,” Cancer 18, 1003-1006 (1965). 8. Smally, S. R., Rubin, J., and Leiferman, K. M., Neurofibrosarcoma and the sign of LeserTrClat, Ca 34, 295-298 (1984). 9. Rigel, D. S., and Jacobs, M. I., Malignant acanthosis nigricans: A review, J. Dermatol. Surg. Oncol. 6, 923-927 (1980). 10. Kierland, R., Cutaneous signs of internal malignancy, South. Med. J. 65, 563-568 (1972). 11. Curth, H. O., Hilberg, H. W., and Machacek, G. F., The site and histology of the cancer associated with malignant acanthosis nigricans, Cancer 15, 364 (1962). 12. Ive, F. A., Metastatic carcinoma cervix with acanthosis nigricans, bullous pemphigoid and hypertrophic pulmonary osteoarthropathy, Proc. R. Sot. Med. 56, 910 (1963).